Background: Cutaneous
melanoma is a highly malignant
tumor which tends to metastasize in the early stage and leads to poor prognosis. Hematogenous and
lymphatic metastasis are common in the dissemination of
melanoma.
Rapamycin, an mTOR inhibitor, was reported to have anti-angiogenic and anti-lymphangiogenic properties. Aim: The aim of this study was to investigate if
rapamycin can inhibit the formation of blood vessels and lymphatic vessels in
melanoma. Methods: A
melanoma xenograft model was generated by subcutaneously transplanting A375 human
melanoma cells into the back of immunodeficient mice. Two weeks after
cell transplantation,
rapamycin was injected intraperitoneally every other day seven times. Then,
tumors were harvested.
Hematoxylin-
eosin (H-E) staining, immunohistochemical staining, Western blot, and quantitative PCR were performed to observe the pathological structure of the
tumor, the distribution of blood vessels and lymphatic vessels, and the expression of mTOR signal pathway,
VEGF-A/VEGFR-2, and
VEGF-C/VEGFR-3. Results: The results showed that CD34(+) blood vessels and LYVE-1(+) lymphatic vessels decreased in the peritumor and intratumor region in
rapamycin-treated
tumors. Expression of p-4EBP1 and p-S6K1
proteins was downregulated. Expression of both
proteins and mRNAs of
VEGF-A/VEGFR-2 and
VEGF-C/VEGFR-3 was downregulated. Conclusion: In conclusion,
rapamycin suppresses angiogenesis and lymphangiogenesis in
melanoma by blocking the mTOR signal pathway and subsequently downregulating the expression of
VEGF-A/VEGFR-2 and
VEGF-C/VEGFR-3. Therefore, targeted
therapy via mTOR signal pathway may control the hematogenous and
lymphatic metastasis of
melanoma, and even prolong patients' survival time.